Protective role of PI3K/Akt pathway during iron-induced oxidative stress in hippocampal neurons

URANGA, ROMINA MARÍA; SÁNCHEZ CAMPOS, SOFIA; SALVADOR, GABRIELA ALEJANDRA

Congreso; VIII International Congress of the Society for Free Radical Biology and Medicine; 2013

Society for Free Radical Biology and Medicine (SFRBM)

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a key component in synaptic plasticity and neuronal survival. The aim of this work was to investigate the participation of the PI3K/Akt pathway and its outcome during mild oxidative stress triggered by iron overload in hippocampal neurons (HT22). The exposure of HT22 cells to different concentrations of Fe2+ (25-200 μM) for 24 h led us to define a mild oxidative injury status (50 μM Fe2+) in which cell lipid peroxidation and cellular oxidant levels increased with no alteration of cellular viability. The presence of iron caused an increase in the phosphorylation levels of Akt. The inhibition of PI3K/Akt pathway (LY294002/Akt inh IV) led to increased levels of oxidative stress, which were prevented in the presence of a constitutively active form of Akt. SOD1 and SOD2 expression strongly decreased during iron-induced oxidative stress in a PI3K-dependent manner. In the presence of iron, glutathione (GSH) levels did not show significant changes, however γ-glutamylcysteine synthetase catalytic subunit (γ-GCSc) levels increased. This rise in γ-GCSc was abolished by LY294002. Results show that  PI3K/Akt pathway plays a key role in neuronal survival by protecting cells from ROS generation through GSH metabolism regulation.